Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

Development of a Pediatric Ebola Predictive Score, Sierra Leone1.

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.

Risk in the "Red Zone": Outcomes for Children Admitted to Ebola Holding Units in Sierra Leone Without Ebola Virus Disease.

We collected data on 1054 children admitted to Ebola Holding Units in Sierra Leone and describe outcomes of 697/1054 children testing negative for Ebola virus disease (EVD) and accompanying caregivers. Case-fatality was 9%; 3/630 (0.5%) children discharged testing negative were readmitted EVD-positive. Nosocomial EVD transmission risk may be lower than feared.

Ebola Virus Disease in Children, Sierra Leone, 2014-2015.

Little is known about potentially modifiable factors in Ebola virus disease in children. We undertook a retrospective cohort study of children <13 years old admitted to 11 Ebola holding units in the Western Area, Sierra Leone, during 2014-2015 to identify factors affecting outcome. Primary outcome was death or discharge after transfer to Ebola treatment centers. All 309 Ebola virus-positive children 2 days-12 years old were included; outcomes were available for 282 (91%). Case-fatality was 57%, and 55% of deaths occurred in Ebola holding units. Blood test results showed hypoglycemia and hepatic/renal dysfunction. Death occurred swiftly (median 3 days after admission) and was associated with younger age and diarrhea. Despite triangulation of information from multiple sources, data availability was limited, and we identified no modifiable factors substantially affecting death. In future Ebola virus disease epidemics, robust, rapid data collection is vital to determine effectiveness of interventions for children.

Pulmonary vascular morphology as an imaging biomarker in chronic thromboembolic pulmonary hypertension.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Viraemia and Ebola virus secretion in survivors of Ebola virus disease in Sierra Leone: a cross-sectional cohort study.

BACKGROUND: In survivors of Ebola virus disease, clinical sequelae including uveitis, arthralgia, and fatigue are common and necessitate systematic follow-up. However, the infection risk to health-care providers is poorly defined. Here we report Ebola virus RT-PCR data for body site and fluid samples from a large cohort of Ebola virus survivors at clinic follow-up. METHODS: In this cross-sectional cohort study, consecutive survivors of Ebola virus disease attending Kerry Town survivor clinic (Freetown, Sierra Leone), who had been discharged from the Kerry Town Ebola treatment unit, were invited to participate. We collected and tested axillary, blood, conjunctival, forehead, mouth, rectal, semen, urine, and vaginal specimens for presence of Ebola virus using RT-PCR. We regarded samples to be positive for Ebola virus disease if the cycle threshold was 40 or lower. We collected demographic data from survivors of their age, sex, time since discharge from the treatment unit, and length of acute admission in the Ebola treatment unit using anonymised standard forms. FINDINGS: Between April 2, and June 16, 2015, of 151 survivors of Ebola virus disease invited to participate, 112 (74%) provided consent. The median age of participants was 21·5 years (IQR 14-31·5) with 34 (30%) participants younger than 16 years. 50 (45%) of 112 participants were male. We tested a total of 555 specimens: 103 from the axilla, 93 from blood, 92 from conjunctiva, 54 from forehead, 105 from mouth, 17 from the rectum, one from semen, 69 from urine, and 21 from the vagina. The median time from Ebola treatment unit discharge to specimen collection was 142 days (IQR 127-159). 15 participants had a total of 74 swabs taken less than 100 days from discharge. The semen sample from one participant tested positive for Ebola virus at 114 days after discharge from the treatment unit; specimens taken from the axilla, blood, conjunctiva, forehead, mouth, rectum, and urine of the same participant tested negative. All specimens from the other 111 participants tested negative. INTERPRETATION: Patients recovering from Ebola virus disease who do not meet the case definition for acute disease pose a low infection risk to health-care providers 6 weeks after clearance of viraemia. Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged. FUNDING: Save the Children International, Public Health England.

T-lymphocyte populations following a period of high volume training in female soccer players.

PURPOSE: To investigate the T-lymphocyte response to a period of increased training volume in trained females compared to habitual activity in female controls. METHODS: Thirteen trained female (19.8 ± 1.9 yrs) soccer players were monitored during a two-week long high volume training period (increased by 39%) and thirteen female untrained (20.5 ± 2.2 yrs) controls were monitored during two-weeks of habitual activity. Blood lymphocytes, collected at rest, were isolated before and after the two-week period. Isolated lymphocytes were assessed for the cell surface expression of the co-receptor CD28, a marker of T-lymphocyte naivety, and CD57 a marker used to identify highly-differentiated T-lymphocytes. Co-expression of these markers was identified on helper CD4(+) and cytotoxic CD8(+) T-lymphocytes. In addition a further population of γδ(+) T-lymphocytes were identified. Plasma was used to determine Cytomegalovirus (CMV) serostatus. RESULTS: No difference was observed in the T-lymphocyte populations following the two-week period of increased volume training. At baseline the number of total CD3(+), cytotoxic CD8(+), naïve (CD8(+) CD28(+) CD57(-)), intermediate (CD8(+) CD28(+) CD57(+)) T-lymphocytes and the number and proportion of γδ(+) T-lymphocytes were greater in the trained compared to the untrained females (p<0.05). The proportion of CD4(+)T-lymphocytes was greater in the untrained compared to the trained (p<0.05), in turn the CD4(+):CD8(+) ratio was also greater in the untrained females (p<0.05). Inclusion of percentage body fat as a covariate removed the main effect of training status in all T-lymphocyte sub-populations, with the exception of the γδ(+) T-lymphocyte population. 8% of the untrained group was defined as positive for CMV whereas 23% of the trained group was positive for CMV. However, CMV was not a significant covariate in the analysis of T-lymphocyte proportions. CONCLUSION: The period of high volume training had no effect on T-lymphocyte populations in trained females. However, baseline training status differences were evident between groups. This indicates that long-term exercise training, as opposed to short-term changes in exercise volume, appears to elicit discernible changes in the composition of the blood T-lymphocyte pool.

EMPHYSEMA QUANTIFICATION IN A MULTI-SCANNER HRCT COHORT USING LOCAL INTENSITY DISTRIBUTIONS.

This article investigates the suitability of local intensity distributions to analyze six emphysema classes in 342 CT scans obtained from 16 sites hosting scanners by 3 vendors and a total of 9 specific models in subjects with Chronic Obstructive Pulmonary Disease (COPD). We propose using kernel density estimation to deal with the inherent sparsity of local intensity histograms obtained from scarcely populated regions of interest. We validate our approach by leave-one-subject-out classification experiments and full-lung analyses. We compare our results with recently published LBP texture-based methodology. We demonstrate the efficacy of using intensity information alone in multi-scanner cohorts, which is a simpler, more intuitive approach.

A study of the headgroup motion of sphingomyelin using 31P NMR and an analytically soluble model.

A 31P NMR investigation has been carried out of the headgroup dynamics of sphingomyelin molecules in bilayers for the L alpha and L beta' phases. The resulting line shapes have been analysed in terms of a reduced-parameter model, using van Faassen's method for obtaining an analytic solution to first-order stochastic differential equations to simulate the line shapes of oriented and non-oriented samples. Our treatment results in good fits to measured data but using fewer parameters than traditional methods. Angles and correlation times (tau parallel and tau perpendicular) describing the geometry and dynamics of the headgroup are obtained by optimising the agreement between simulated and experimental data. The results are contrasted with those obtained for the lecithins DMPC and DPPC using a similar analysis. Not only are tau parallel and tau perpendicular now equal in value for the L alpha phase, but this value is also found to be nearly four times larger than the longest correlation time for the lecithins. We interpret this as evidence of inter- and intramolecular hydrogen bonding in the L(alpha) phase of sphingomyelin. In the L beta' phase of sphingomyelin, however, although tau(parallel) and tau(perpendicular) remain equal their value is now 32% smaller than that of the lecithins in the same phase. This indicates less difference between the fluidities in the headgroup region of the two phases of sphingomyelin as compared to that of the lecithins. Another significant difference between the L beta' phases is that the tilt angle for sphingomyelin is found to be nearly twice as large as for the lecithins. We argue that these combined observations point to the existence of hydrogen bonding in this phase also. Again in contrast to our previous work on lecithins, our results provide evidence of a negative diamagnetic anisotropy in sphingomyelin molecules, even in the L beta' phase. This is provided for in our model by the assumption that our unoriented samples consist of prolate ellipsoidal liposomes whose major axes are oriented parallel to the static magnetic field. The apparently different diamagnetic behaviour of sphingomyelin in the present work is due to the higher static field used rather than any intrinsic difference in this respect between sphingomyelin and the lecithins DMPC and DPPC.

The natural history of trunk list, its associated disability and the influence of McKenzie management.

Lumbosacral list is a clinical sign that is frequently associated with low back pain and intervertebral disc lesions. This study examines the influence of McKenzie management on the natural history of trunk list. Patients with trunk list and low back pain were randomised into two groups: a control group receiving non-specific back massage and general back care advice, and a group treated according to the McKenzie protocol. Trunk list was measured over a period of 90 days and patients completed Oswestry Disability Questionnaires. There was a significantly greater resolution of list after 90 days in the group receiving McKenzie treatment compared to the control group. There was poor correlation between list magnitude and Oswestry scores. These data support previous observations that trunk list is not necessarily related to the degree of physical disability. The McKenzie method of assessment and treatment may assist in the resolution of trunk list, but it was ineffective in improving clinical condition.

A comparison of methods for measuring trunk list. A simple plumbline is the best.

STUDY DESIGN: Trunk list was measured using three different techniques to compare accuracy, precision, and ease of use. OBJECTIVE: To obtain a reproducible technique for further studies of the nature, cause, and clinical relevance of trunk list. SUMMARY OF BACKGROUND DATA: Gravity-induced trunk list is a clinical sign that is frequently observed in patients with low back pain and has been associated with intervertebral disc lesions. METHODS: Patients with trunk list participated in a comparison of three techniques to determine list magnitude and direction. Paired measurements of trunk list were obtained from each patient using three techniques: a plumbline, a projected shadow, and the 3SPACE Isotrak (McDonnell Douglas Electronics Company, Colchester, VT). In addition, intra- and interobserver reliability of list measurement was assessed by comparison of paired measurements by each of two observers. RESULTS: List measurements assessed by the plumbline and the projected shadow techniques were not significantly different, but the Isotrak produced data that differed significantly (P < 0.05) from both of these techniques. Comparison of intra- and interobserver repeatability of list measurement using the plumbline technique indicated no significant difference between repeated measures by each observer or between two observers. CONCLUSIONS: A plumbline is the most useful instrument for measuring static trunk list, but its limitations and the need for standardization of measurement technique must be recognized.

Placental transport and fetal utilization of leucine in a model of fetal growth retardation.

Placental transport and fetal utilization of leucine were studied at 130 days of gestation in six control ewes and in seven ewes in which intrauterine growth retardation (IUGR) had been induced by exposure to heat stress. Leucine fluxes were measured during simultaneous intravenous infusion of L-[1-13C]leucine into the mother and L-[1-14C] leucine into the fetus. In the IUGR group, the following leucine fluxes, expressed as micromol/min/kg fetus, were reduced compared with control: net uterine uptake (3.44 vs. 8.56, P<0.01), uteroplacental utilization (0.0 vs. 4.7, P<0.01), fetal disposal rate (6.4 vs. 8.9, P<0.001), flux from placenta to fetus (5.0 vs. 7.1, P<0.01), direct transport from mother to fetus (1.6 vs. 3.4, P<0.01), flux from fetus to placenta (1.5 vs. 3.2, P<0.001), and oxidation of fetal leucine by fetus plus placenta (2.1 vs. 3.2, P<0.02). Uterine uptake, uteroplacental utilization, and direct transport were also significantly reduced per gram placenta. We conclude that maternal leucine flux into the IUGR placenta is markedly reduced. Most of the reduced flux is routed into fetal metabolism via a decrease in placental leucine utilization and a decrease in the leucine flux from fetus to placenta.

Problems with tracheoesophageal fistula voice restoration in totally laryngectomized patients. A review of 95 cases.

OBJECTIVES: Tracheoesophageal fistula (TEF) construction, performed during or after total laryngectomy, is used for voice and speech restoration but has been associated with mild to severe complications. Our goal was to study the successes and complications in the application of this technique to restore voice function after laryngectomy in 95 consecutive patients. RESEARCH DESIGN: Retrospective cohort study with a mean follow-up time of 3.5 years. SETTING: Five medical facilities in northern California: the Veterans Affairs Medical Centers in San Francisco and Martinez, the Kaiser Permanente Medical Center in Oakland, and private practice offices in San Francisco and Pinole. PATIENTS: Ninety-five patients (90 men and five women) who had undergone total laryngectomy with subsequent or primary TEF construction. Patients' ages ranged from 35 to 80 years. INTERVENTIONS: Three- or two-layer closure was used, depending on whether TEF construction was done as a secondary or a primary procedure. Most patients underwent radiation therapy, and most used surface or intraoral electrolarynx devices before TEF construction. Insufflation tests were performed by clinicians, or self-insufflation tests were performed by the patient. Patients' voices were recorded and analyzed. In many cases, respiratory and pulmonary function studies were performed before and after total laryngectomy or TEF. Blom-Singer and Groningen voice prostheses were used. MAIN OUTCOME MEASURES: Voice restoration was considered successful when the patient was able to communicate effectively via the TEF. RESULTS: Approximately 92% of patients who underwent TEF construction and had voice prostheses placed were considered to be successfully rehabilitated. Complications ranged from mild to severe and included problems with predictive values obtained during insufflation, fistula retention, TEF angulation shifts, fungal colonization of the prosthesis, valve retention problems, difficulty with digital occlusion, pressure necrosis, postradiation necrosis, dysphagia, phonatory gagging, emesis, gastric distention, pouching, stenosis, infection, hypertrophy, shunt insufficiency, persistent spasm, myotomy, inadvertent fistula closure, and aspiration of the prosthesis. CONCLUSIONS: Acoustic measures indicate that speech produced with the TEF compares better with normal laryngeal speech than does esophageal or electronic speech. Thus, TEF should remain the preferred procedure to rehabilitate patients undergoing total laryngectomy.

Ventricular dysphonia: a profile of 40 cases.

Ventricular dysphonia is a poorly understood disorder involving ventricular fold participation during phonation. A population of ventricular dysphonia patients was evaluated using phonatory function studies such as laryngovideostroboscopy, advanced acoustic analysis, and electroglottography to identify shared epidemiologic characteristics and to discuss possible neuromuscular mechanisms and causes. Forty patients with ventricular dysphonia were studied and epidemiologic, acoustic, and histologic data were analyzed. In almost all cases, the authors found abnormalities affecting the glottis caused by a related medical condition. The abnormalities included true vocal cord (TVC) aperiodicity in 100% of the patients, TVC asymmetry in 65%, a laryngeal mass or foreign body (usually Teflon) in 35%, TVC erythema or edema in 32.5%, and TVC bowing in 22.5%. Ventricular dysphonia seems to be primarily a compensatory mechanism for glottic dysfunction. Therapy is based on identifying and correcting the underlying abnormalities. Laryngovideostroboscopy is a particularly important tool in examining chronic dysphonia.

Fine-needle aspiration in the diagnosis of salivary gland disorders in the community hospital setting.

From 1983 to 1988, 47 patients with salivary gland disorders were assessed with fine-needle aspiration (FNA) before surgery. The preoperative fine-needle diagnoses were then compared with the postoperative pathologic findings. In the same period, 63 patients from two other community hospitals who had been evaluated preoperatively with FNA were studied retrospectively. The overall sensitivity of FNA for salivary neoplasms was 80.6%. Fine-needle aspiration was more sensitive in identifying benign tumors (88.4%) than malignant neoplasms (58.3%) and was least sensitive in identifying nonneoplastic salivary diseases (35.3%). Pleomorphic adenomas were correctly identified preoperatively in 96.2% of cases, whereas for malignant neoplasms, the diagnostic accuracy was highest for mucoepidermoid carcinoma (50%). To demonstrate the strengths of FNA as a diagnostic tool, as well as to delineate its limitations, we present our 5-year experience. Our FNA results are similar to those reported by the major European and American referral centers. Because our medical centers are community based, our results may more accurately reflect those seen by otolaryngologists in private practice. To date, no evidence of tumor seeding along the FNA tract has been reported.

Steroid receptors in surgical pathology. With special reference to small mammographically detected breast lesions.

The cellular receptors for estrogen, progesterone, and other steroid hormones appear in the cytosol fraction of homogenated specimens of hormonal target tissues. These receptors have traditionally been detected and quantitated by biochemical techniques that involve binding tritium-labelled marker steroids to the receptor proteins. An important recent development has been the creation of various monoclonal antibody reagents that specifically recognize antigenic determinants on receptor molecules.

Intertester reliability of the Modified Anterior Drawer (Lachman) Test for anterior cruciate ligament laxity.

Eight therapists each examined 16 subjects (14 with documented ACL pathology, two normal subjects) in a single session. Instrumented anterior laxity measurements were performed bilaterally on all subjects prior to testing. Therapists assessed the degree of anterior tibial translation on a visual analogue scale, and indicated whether the nominated knee tested positive or negative using the Lachman test. Intertester reliability in assessing anterior translation was low. Correlation between the overall therapists' translation measurements and the arthrometer was moderate. Intertester reliability in indicating whether the nominated knee tested positive or negative was low. These findings suggest that greater expertise is necessary for therapists to reliably use the Lachman test as an assessment procedure in evaluation of the injured knee.

A technique for fabrication of a custom tracheostomy prosthesis.

A technique is described for using an endotracheal tube to make an impression of the intratracheal anatomy for fabrication of a custom-fitted tracheostomy prosthesis.